SORBET: Automated cell-neighborhood analysis of spatial transcriptomics or proteomics for interpretable sample classification via GNN.

Spatially resolved transcriptomics or proteomics data have the potential to contribute fundamental insights into the mechanisms underlying physiologic and pathological processes. However, analysis of these data capable of relating spatial information, multiplexed markers, and their observed phenotypes remains technically challenging. To analyze these relationships, we developed SORBET, a deep learning framework that leverages recent advances in graph neural networks (GNN). We apply SORBET to predict tissue phenotypes, such as response to immunotherapy, across different disease processes and different technologies including both spatial proteomics and transcriptomics methods. Our results show that SORBET accurately learns biologically meaningful relationships across distinct tissue structures and data acquisition methods. Furthermore, we demonstrate that SORBET facilitates understanding of the spatially-resolved biological mechanisms underlying the inferred phenotypes. In sum, our method facilitates mapping between the rich spatial and marker information acquired from spatial 'omics technologies to emergent biological phenotypes. Moreover, we provide novel techniques for identifying the biological processes that comprise the predicted phenotypes.

Biophysical prediction of protein-peptide interactions and signaling networks using machine learning.

In mammalian cells, much of signal transduction is mediated by weak protein-protein interactions between globular peptide-binding domains (PBDs) and unstructured peptidic motifs in partner proteins. The number and diversity of these PBDs (over 1,800 are known), their low binding affinities and the sensitivity of binding properties to minor sequence variation represent a substantial challenge to experimental and computational analysis of PBD specificity and the networks PBDs create. Here, we introduce a bespoke machine-learning approach, hierarchical statistical mechanical modeling (HSM), capable of accurately predicting the affinities of PBD-peptide interactions across multiple protein families. By synthesizing biophysical priors within a modern machine-learning framework, HSM outperforms existing computational methods and high-throughput experimental assays. HSM models are interpretable in familiar biophysical terms at three spatial scales: the energetics of protein-peptide binding, the multidentate organization of protein-protein interactions and the global architecture of signaling networks.

Awake Surgical Management of Third Ventricular Tumors: A Preliminary Safety, Feasibility, and Clinical Applications Study.

BACKGROUND: Endoscopic and microneurosurgical approaches to third ventricular lesions are commonly performed under general anesthesia. OBJECTIVE: To report our initial experience with awake transsulcal parafascicular corridor surgery (TPCS) of the third ventricle and its safety, feasibility, and limitations. METHODS: A total of 12 cases are reviewed: 6 colloid cysts, 2 central neurocytomas, 1 papillary craniopharyngioma, 1 basal ganglia glioblastoma, 1 thalamic glioblastoma, and 1 ependymal cyst. Lesions were approached using TPCS through the superior frontal sulcus. Pre-, intra-, and postoperative neurocognitive (NC) testing were performed on all patients. RESULTS: No cases required conversion to general anesthesia. Awake anesthesia changed intraoperative management in 4/12 cases with intraoperative cognitive changes that required port re-positioning; 3/4 recovered. Average length of stay (LOS) was 6.1 d ± 6.6. Excluding 3 outliers who had preoperative NC impairment, the average LOS was 2.5 d ± 1.2. Average operative time was 3.00 h ± 0.44. Average awake anesthesia time was 5.05 h ± 0.54. There were no mortalities. CONCLUSION: This report demonstrated the feasibility and safety of awake third ventricular surgery, and was not limited by pathology, size, or vascularity. The most significant factor impacting LOS was preoperative NC deficit. The most significant risk factor predicting a permanent NC deficit was preoperative 2/3 domain impairment combined with radiologic evidence of invasion of limbic structures - defined as a "NC resilience/reserve" in our surgical algorithm. Larger efficacy studies will be required to demonstrate the validity of the algorithm and impact on long-term cognitive outcomes, as well as generalizability of awake TPCS for third ventricular surgery.

She looks sad, but he looks mad: the effects of age, gender, and ambiguity on emotion perception.

This study investigated how target sex, target age, and expressive ambiguity influence emotion perception. Undergraduate participants (N = 192) watched morphed video clips of eight child and eight adult facial expressions shifting from neutral to either sadness or anger. Participants were asked to stop the video clip when they first saw an emotion appear (perceptual sensitivity) and were asked to identify the emotion that they saw (accuracy). Results indicate that female participants identified sad expressions sooner in female targets than in male targets. Participants were also more accurate identifying angry facial expressions by male children than by female children. Findings are discussed in terms of the effects of ambiguity, gender, and age on the perception of emotional expressions.

Nuclear factor κB mediates suppression of canonical transient receptor potential 6 expression by reactive oxygen species and protein kinase C in kidney cells.

This study was carried out to explore the molecular mechanism for down-regulation of TRPC6 expression in the reactive oxygen species (ROS)/PKC signaling in kidney cells. In cultured human mesangial cells, H2O2 and TNF-α inhibited TRPC6 mRNA expression in a time-dependent manner. Inhibition of NF-κB reversed both H2O2- and phorbol 12-myristate 13-acetate (PMA)-induced decrease in TRPC6 protein expression. Activation of NF-κB by knocking down IκBα using siRNA could mimic the suppressive effect of ROS/PKC on TRPC6. a Ca(2+) imaging study showed that activation and inhibition of NF-κB significantly decreased and increased the TRPC6-mediated Ca(2+) entry, respectively. Further experiments showed that PMA, but not its inactive analog 4α-phorbol 12, 13-didecanoate (4α-PDD), caused phosphorylation of IκBα and stimulated the nuclear translocation of NF-κB p50 and p65 subunits. The PMA-dependent IκBα phosphorylation was significantly inhibited by Gö6976. Electrophoretic mobility shift assay revealed that PMA stimulated DNA binding activity of NF-κB. Furthermore, specific knockdown of p65, but not p50, prevented an H2O2 inhibitory effect on TRPC6 protein expression, suggesting p65 as a predominant NF-κB subunit repressing TRPC6. In agreement with a major role of p65, chromatin immunoprecipitation assays showed that PMA treatment induced p65 binding to the TRPC6 promoter. Moreover, PMA treatment increased the association of p65 with histone deacetylase (HDAC) and decreased histone acetylation at the TRPC6 promoter. Consistently, knockdown of HDAC2 by siRNA or inhibition of HDAC with trichostatin A prevented a H2O2-induced decrease in TRPC6 mRNA and protein expressions, respectively. Taken together, our findings imply an important role of NF-κB in a negative regulation of TRPC6 expression at the gene transcription level in kidney cells.

Protistan predation affects trichloroethene biodegradation in a bedrock aquifer.

Despite extensive research on the bottom-up force of resource availability (e.g., electron donors and acceptors), slow biodegradation rates and stalling at cis-dichloroethene (cDCE) and vinyl chloride continue to be observed in aquifers contaminated with trichloroethene (TCE). The objective of this research was to gauge the impact of the top-down force of protistan predation on TCE biodegradation in laboratory microcosms. When indigenous bacteria from an electron donor-limited TCE-contaminated bedrock aquifer were present, the indigenous protists inhibited reductive dechlorination altogether. The presence of protists during organic carbon-amended conditions caused the bacteria to elongate (length:width, > or =10:1), but reductive dechlorination was still inhibited. When a commercially available dechlorinating bacterial culture and an organic carbon amendment were added in he presence of protists, the elongated bacteria predominated and reductive dechlorination stalled at cDCE. When protists were removed under organic carbon-amended conditions, reductive dechlorination stalled at cDCE, whereas in the presence organic carbon and bacterial amendments, the total chlorinated ethene concentration decreased, indicating TCE was converted to ethene and/or CO2. The data suggested that indigenous protists grazed dechlorinators to extremely low levels, inhibiting dechlorination altogether. Hence, in situ bioremediation/bioaugmentation may not be successful in mineralizing TCE unless the top-down force of protistan predation is inhibited.

Use of text messaging to enhance compliance with the accreditation council for graduate medical education resident duty hour requirements.

PURPOSE: Recently, the Accreditation Council for Graduate Medical Education (ACGME) has developed and enforced a complex set of regulations limiting resident duty hours (RDHs). One potential method to comply with these stringent regulations and better document resident work hours would be to use text message (TM)/short message service (SMS), allowing rapid, inexpensive, and interactive 2-way delivery of information. The purpose of this study was to document the successful implementation of TM to enhance compliance with the ACGME RDH regulations. METHODS: Our TM system uses TSHEETS (TS; Meridian, Ohio), which is an online time- and labor-management service. After our general surgical residents were registered with the system, the documentation of entry into (texting "t start" to a predetermined number) and exit out of (texting "t stop" to the same number) the hospital could easily be accomplished. The goals of this pilot study were to determine (1) the feasibility of implementing a program such as this and (2) if use of such a program was associated with high resident satisfaction and improved compliance. RESULTS: We registered 39 residents with TS. Within 3 days, compliance rose from 76.9% to 96.2%. After implementation of TM reminders, compliance increased to 100%. A time-tracking resident satisfaction survey was distributed after 8 weeks of data collection. Twenty six of 39 (67%) residents participated in the survey, with 25 (96%) being more satisfied with the current application as compared with either of the previous (manual or swipe card) systems, specifically regarding ease of use and overall ACGME RDH compliance. Self-reported resident scores of their ability to be compliant with ACGME RDH before versus after implementation increased from 47% to 75% (p < 0.05). CONCLUSIONS: We were able to implement successfully a novel technique for ACGME RDH documentation and compliance in a general surgery residency program through the use of TM; this approach employed a state-of-the-art time-tracking method that was associated with high levels of resident work-hour compliance and overall satisfaction.

Expedient pulmonary embolectomy for acute pulmonary embolism: improved outcomes.

Indications regarding surgical pulmonary embolectomy for treatment of submassive/massive acute pulmonary embolism remain controversial. An institutional experience with pulmonary embolectomy for acute pulmonary embolism (APE) was reviewed. A retrospective analysis of all patients undergoing pulmonary embolectomy for APE from September 2004 to January 2007 was conducted. Demographic data, clinical presentation and outcomes were analyzed. Fifteen patients underwent surgery for APE over a period of 27 months [average age 59.6 (range 35-89) years, (seven male, eight female)]. Six (40%) patients were admitted with known APE and nine patients exhibited post admission APE (seven - after surgical procedures, two - after cerebrovascular accident). Clinical presentation included dyspnea (86.67%), hemodynamic instability requiring continuous vasopressor support (40%), echocardiographic evidence of right ventricular dilatation (80%). Ten patients undergoing early/expedient embolectomy all survived while delayed surgery in the other five patients (>24 h) was associated with 60% mortality. Expanding indications for early surgical pulmonary embolectomy has stemmed from reliable echocardiographic identification of right ventricular compromise and recognition of these findings as harbingers of subsequent hemodynamic embarrassment. Our series underscores the benefit of early consideration and performance of pulmonary embolectomy in these critically ill patients.

Unexpected right hemisphere language representation identified by the intracarotid amobarbital procedure in right-handed epilepsy surgery candidates.

The intracarotid amobarbital procedure (IAP) is used for language lateralization in the presurgical evaluation for intractable epilepsy. Some epilepsy surgical centers forgo IAP for right temporal lobectomies in right-handed patients with no personal/family history of left-handedness, implying that right hemisphere language representation does not occur in these patients. To test this hypothesis, a retrospective analysis was performed on 156 consecutive epilepsy surgery candidates who underwent IAP. Of the 156 candidates, 122 were right-handed, and 55 of the 122 demonstrated right hemisphere seizure focus. Right hemisphere language representation was found in 22 of 55 patients, with two demonstrating significant right hemisphere language despite a right hemisphere seizure focus and no family history of left-handedness. Only 1 of 156 patients undergoing IAP experienced permanent neurological complications. Although relatively uncommon, right hemisphere language representation may occur more frequently than complications from cerebral angiography and, therefore, presurgical IAP is recommended for all epilepsy surgery candidates regardless of handedness to minimize the risk of severe language decline.

Circadian rhythm has no effect on mortality in coronary artery bypass surgery.

BACKGROUND: The circadian variation that affects atherosclerosis has not been studied in the surgical patient. The circadian variation in mortality dependent on the time of surgery was examined in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: A 4-year retrospective review of all CABG patients (n = 3140) from 1999 to 2002 was undertaken. The patients were divided into elective, urgent, and emergency cases. The cases were subdivided according to the start time of the operation as morning (7 AM to 2 PM = AM), afternoon (2 PM to 8 PM = AF), and night (8 PM to 7 AM = NT). The outcome was mortality within 30 days and compared for three different time frames: (1) AM versus AF (2) AM versus NT (3) AF versus NT for each prioritized group. Risk factors and number of anastamoses were compared for each group. Sigma Statistical package and Z-test for two group comparison were used for analysis. t-Test was used to compare age and ejection fraction. RESULTS: No statistically significant difference in mortality was observed for the elective and urgent groups for each of the time periods compared. The emergency cases had significantly increased deaths in the AM and NT compared to the AF (p < 0.01 and p < 0.05, respectively). There was no statistically significant difference with respect to age, gender, number of anastamoses performed, ejection fraction, and preoperative risk factors between groups. CONCLUSIONS: The mortality for nonemergent CABG is independent of the timing of surgery. Circadian variation does not influence the outcome in cardiac surgical patients.

Cardiac valve papillary fibroelastoma: surgical excision for revealed or potential embolization.

Cardiac papillary fibroelastomas (CPF) are benign endocardial papillomas commonly formed from valve endothelium. The majority of tumors are found on the left side of the heart, with only a few case reports of pulmonary valve fibroelastomas. We report here a case of pulmonary valve papillary fibroelastoma that was successfully managed with simple excision of the mass.

Telemetric recording of intrapleural pressure.

BACKGROUND: Monitoring of intrapleural pressure (IPP) is used for evaluation of lung function in a number of pathophysiological conditions. We describe a telemetric method of non-invasive monitoring of the IPP in conscious animals intermittently or continuously for a prolonged period of time. MATERIALS AND METHODS: After IACUC approval, six mongrel dogs were used for the study. After sedation, each dog was intubated and anesthetized using 0.5% Isoflurane. A telemetric implant model TL11M2-D70-PCT from Data Science International was secured subcutaneously. The pressure sensor tip of the catheter from the implant was inserted into the pleural space, and the catheter was secured with sutures. The IPP signals were recorded at a sampling rate of 100 points/second for 30 to 60 min daily for 4 days. From these recordings, the total mean negative IPP (mmHg), and the total mean negative IPP for a standard time of 30 min were calculated. In addition, the actual inspiratory and expiratory pressures were also measured from stable recording of the IPP waveforms. RESULTS: In six dogs, the total mean +/- SD negative IPP was -10.8 +/- 10.6 mmHg. After normalizing with respect to acquisition time it was -13.2 +/- 11.2 mmHg/min. The actual inspiratory pressure was -19.7 +/- 15.3, and the expiratory pressure was -11.0 +/- 12.9. CONCLUSIONS: Our study demonstrates that telemetric monitoring of IPP can be performed reliably and non-invasively in conscious experimental animals. The values for IPP in our study are compatible with the results of other investigators who used different methods of IPP measurement. Further work may show this method to be helpful in understanding the pathophysiology of various breathing disorders.

Bed occupancy, turnover intervals and MRSA rates in English hospitals.

This article (a follow on from an article concentrating on Northern Ireland) examines the relationship between percentage bed occupancy (PO), turnover interval (TI) and methicillin-resistant Staphylococcus aureus (MRSA) rates in the acute beds of specialist English hospital trusts and describes the TI and levels of bed occupancy. The data were collected from publicly available data: MRSA rates of blood-borne infection per 1000 bed days from the Department of Health; average length of stay from Hospital Episode Statistics; and percentage occupancy from the Department of Health Hospital Activity statistics were used. Pearson's Correlation coefficients were used as basis for inferential analysis. The mean TI for all trusts was as 0.94 days, median 0.95 days. Twenty percent of trusts had TIs, on average, of less than 0.58 days (13.9 hours) and 10% had a TI less than 0.32 days (7.6 hours). The mean PO was 84.98% and the median was 84.76%. Seventy percent of the trusts exceeded the recommended 82% bed occupancy. The inference from this study is that there is a relationship between TI and PO and rate of MRSA infection in specialist English hospitals and that PO rates are at a level which may interfere with good infection control procedures.

Pseudoaneurysms of the ascending aorta following coronary artery bypass surgery.

BACKGROUND: Ascending aortic pseudoaneurysms following prior cardiac procedures are a rare entity. We reviewed our institutional experience given the isolated case reports in the literature. METHODS: A 10-year retrospective review identified 5 patients who underwent ascending aorta pseudoaneurysm repair. There were 3 women and 2 men with a median age of 70 years (range 63 to 79 years). Median duration from initial CABG to pseudoaneurysm repair was 5 years (range 5 months to 18 years). The clinical presentations included dyspnoea (2 patients), chest pain, fever of unknown origin, and a pulsatile mass. Four patients underwent urgent investigation and surgery. Diagnosis was established via CT scan (3 patients), transesophageal echocardiogram (1 patient), and MRA (1 patient). Two patients had a prior history of sternal wound infection. RESULTS: Mortality was 60%. One survivor experienced a stroke. The etiology was prior cannulation site in 4 cases and vein graft anastamotic site in 1. Necrotic aortic tissue was noticed in 2 cases. Aortic tissue cultures were negative in all the patients. Cardiopulmonary bypass was established prior to sternotomy in 4 cases and 1 case was performed off-pump. Inadvertent rupture of the pseudoaneurysm (without exsanguination) occurred in 2 cases following sternotomy. Repair was performed with bovine pericardial patch in 2 cases and plication in 3 cases. CONCLUSION: This highlights the varied presentation, necessity for urgent diagnosis and repair with a high operative mortality due to the late presentation. Aggressive diagnosis should be sought and consideration should be given to catheter-based interventions for initial treatment.

Bed occupancy, turnover interval and MRSA rates in Northern Ireland.

The data describe bed turnover intervals (TI), bed percentage occupancy (PO) and methicillin-resistant Staphylococcus aureus (MRSA) rates per 1000 bed days of patient episodes. It was collected from annual hospital statistics in Northern Ireland (NI) and from the Communicable Diseases Surveillance Centre (CDSC) NI. The descriptive data show 6 of the general 11 surgical Trusts, out of a total of 12 Trusts examined, had PO greater than 85%; and all 11 medical facilities in these Trusts had occupancy rates greater than 85%. A significant correlation was established between turnover interval and MRSA per 1000 bed days of patient episodes in acute services beds. The correlation of PO with MRSA rates was 0.49 (ns). The conclusions drawn from the study are that in many Trusts the rates of bed occupancy for general surgery and general medicine is in excess of national guidelines and rapid turnover of patients is related to rates of MRSA infection. The implications for nurses and managers are discussed.

Open heart surgery in patients 85 years and older.

BACKGROUND: There has been an increase in the number of elderly patients considered for cardiac surgery. Several reports have documented acceptable morbidity and mortality in patients 80 years and older. The results from surgical patients 85 years and older were analyzed. METHODS: The records of 89 consecutive patients 85 years and older having cardiac operations between June 1993 and May 1999 were retrospectively reviewed. For purposes of statistical analysis follow-up was considered as a minimum of one office visit to the surgeon, cardiologist, or internist at least 1 month postoperatively. RESULTS: Eighty-seven patients underwent coronary artery grafting and two patients had mitral valve replacement. Follow-up was 100% complete. The operative mortality rate was 12.3%; probability of in-hospital death was 8.2%; risk-adjusted mortality rate was 3.2%. The complication rate was 31.5%. The actuarial 1-, 3-, and 5-year survivals were as follows: 75%, 67%, and 40%. Multivariate predictors of 30-day mortality were preoperative EF, less than 30% (p = 0.029) and postoperative renal failure (p = 0.0039). CONCLUSIONS: Cardiac surgery can be performed in patients 85 years and older with good results. There is an associated prolonged hospital stay for elderly patients. Consistent successful outcomes can be expected in this patient population with selective criteria identifying risk factors.

Telemetrically monitored arrhythmogenic effects of doxorubicin in a dog model of heart failure.

A model of chronic heart failure has been induced in dogs by repeated intracoronary infusion of doxorubicin, which is an antineoplastic medication that has dose-limiting cardiotoxic side effects. Although many of the dogs receiving doxorubicin develop typical signs of dilated cardiomypathy over 4-6 weeks, some of them suddenly die before completing the four weekly infusions of the drug. The present study was undertaken to determine whether such sudden death may be caused by the development of fatal arrhythmias during doxorubicin treatment. This was assessed by telemetrically monitoring the EKG of seven dogs, which received intracoronary infusion of 1 mg/kg doxorubicin given in four divided weekly doses. The recordings were obtained for 8-10 h on alternate days up to 4 weeks. Echo-cardiographic recordings were obtained once a week. The acute effects with each infusion of doxorubicin included a significant increase in heart rate, and no significant change in QRS complex. The cumulative prolonged effects of doxorubicin included slight reduction in QRS amplitude and duration, and marked arrhythmic changes. Four out of seven dogs showed a spectrum of arrhythmic events such as single or groups of premature ventricular complexes (PVCs), bigeminy, ventricular tachycardia (VTAC), ventricular fibrillations (VFIB), and asystole. All dogs did not show each of the events listed above and the same dog did not show all the events all the time. One of these four dogs developed VFIB for 25 min and then asystole leading to sudden death. These studies conclusively showed that fatal arrhythmias develop in some of the dogs receiving doxorubicin treatment accounting for the sporadic incidence of sudden death. Prophylactic treatment with antiarrhythmic agents may prevent such adverse events.

Correlation of blood volume values and pulmonary artery catheter measurements.

OBJECTIVE: To correlate the values generated by direct total blood volume measurement with pulmonary artery catheter parameters and commonly used laboratory values in the management of critically ill patients. METHODS: This study was carried out at the Lutheran Medical Center, Brooklyn, New York, United States of America, during the period 1998-1999. We prospectively correlated the total blood volume (TBV) values generated by the blood volume analyzer (BVA)-100 using I131-tagged albumin, with the values obtained from pulmonary artery catheter (PAC) of central venous pressure, pulmonary capillary wedge pressure, cardiac output, and with laboratory values of hematocrit, lactate, arterial blood gas and mixed venous blood, in critically ill patients. Twenty-four intensive care unit (ICU) patients were studied. INCLUSION CRITERIA: Admission to the intensive care, pulmonary artery catheter insertion and (APACHE) II Acute Physiology and Chronic Health Evaluation score of 8-30 (mean=17.875). EXCLUSION CRITERIA: Pediatric patients, hemodynamically normal or stable patients, pregnancy, and critically ill patients that were managed in an ICU setting without PAC catheter. Height and weight were recorded. After the collection of an initial blood sample (5 cc), one cc of I131-tagged albumin (15-25 microcuries) was injected using a patented syringe. Five venous samples were collected after the isotope injection. RESULTS: The collection times were entered into the BVA-100. Hematocrit measurements were performed in duplicate. Blood samples were centrifuged and one ml from the plasma of each sample was pipetted (in duplicate) into the sample tube then placed into the BVA-100. The results showed that the TBV did not correlate with either pulmonary capillary wedge pressure or central venous pressure, and except for the cardiac output, there is no correlation between pulmonary capillary wedge pressure readings or TBV results and the other parameters considered in this study. CONCLUSION: This method can be released from the research fields and can be safely incorporated into the clinical arena. It provides an accurate assessment of the volume status in intensive care unit patients.